191MO - KEYNOTE-355: Outcomes in patients who discontinued chemotherapy before pembrolizumab and in patients with immune-mediated AEs

Background

In the phase III KEYNOTE-355 study (NCT02819518), first-line treatment with pembro + chemo resulted in statistically significant and clinically meaningful improvements in PFS and OS versus placebo + chemo in patients (pts) with advanced TNBC with PD-L1 combined positive score (CPS) ≥10. We report efficacy outcomes from the KEYNOTE-355 final analysis for pts who had disease control and discontinued chemo before pembro and for pts who experienced immune-mediated AEs.

Methods

Pts with untreated locally recurrent inoperable or metastatic TNBC were randomized 2:1 to pembro (200 mg Q3W) or placebo for 35 cycles in combination with chemo (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). Treatment continued until progression, intolerable toxicity, or (for pembro/placebo) completion of 35 cycles; pts could discontinue chemo independently of pembro/placebo (and vice versa). In this analysis, PFS per RECIST v1.1 by BICR and OS were evaluated in (a) pts who received pembro + chemo, achieved a best objective response of CR, PR, or SD lasting ≥24 wk, and received their last dose of chemo >21 days before their last dose of pembro, and (b) pts who received pembro + chemo and experienced ≥1 immune-mediated AEs (per a list of preferred terms compiled from the CTCAE v4.0).

Results

Pts were randomized to pembro + chemo (n=566) or placebo + chemo (n=281). At data cutoff (June 15, 2021), 317 pts in the pembro + chemo group had CR, PR, or SD ≥24 wk. Among these pts, discontinutation of chemo before pembro was associated with similar efficacy to that in the overall population, irrespective of tumor PD-L1 CPS (Table). Similarly, there was evidence of antitumor activity in pts who had immune-mediated AEs, overall and by tumor PD-L1 CPS (Table).

Conclusions

In this analysis of outcomes among pts who received pembro + chemo in the KEYNOTE-355 study, there was evidence for efficacy of pembro + chemo regardless of discontinuation of chemo before pembro or occurrence of immune-mediated AEs.

Table: 191MO

NR=not reached.^aPer Kaplan-Meier method.

Clinical trial identification

NCT02819518.

Editorial acknowledgement

Medical writing assistance was provided by Sonia Mohinta, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly, Roche/Genentech, Macrogenics, OBI, Merck, Eisai, Immunomedics, Daiichi Sankyo, Seattle Genetics, and Odonate; Financial Interests, Personal, Other, Consultant: Samsung and Puma; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and Macrogenics. D.W. Cescon: Financial Interests, Personal, Advisory Role: AstraZeneca, Exact Sciences, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer and Roche; Financial Interests, Institutional, Funding: GlaxoSmithKline, Inivata, Merck, Pfizer and Roche; Financial Interests, Personal, Other, member of a trial steering committee: AstraZeneca, Merck and GlaxoSmithKline. S. Im: Financial Interests, Personal, Other, Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Pfizer; Financial Interests, Personal, Other, Advisory / Consultancy: Amgen, Eisai, Hanmi, Ildong, MediPactor, Novartis, Roche. M. Md Yusof: Financial Interests, Personal, Other, Received honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, MSD, Specialised Therapeutics, Zuellig Pharma, Novartis, Pfizer, Roche, Eisai, Celgene; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Arcus, Genentech, Mundi Pharma, Novartis, Pfizer, Roche. C.E. Gallardo Araneda: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Funding: Novartis pharma SAS; Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Roche. C.H. Barrios: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Eisai Europe Ltd.; GlaxoSmithKline; Novartis pharma SAS; Pfizer Pharmaceuticals Israel; Roche/Genentech; Financial Interests, Personal, Funding: AB Science; Abraxis BioScience; Amgen; Asana Biosciences; Astellas Pharma; AstraZeneca; Biomarin; Boehringer Ingelheim; Bristol Myers Squibb; Daiichi Sankyo; Exelixis; GlaxoSmithKline; ImClone Systems; Investigator in AbbVie-sponsored cl. trials; LEO Phar. N. Turner: Financial Interests, Personal, Other, Received honoraria: Pfizer Inc.; Financial Interests, Personal, Advisory Role: Pfizer Inc.; Financial Interests, Personal, Funding: Servier, Pfizer Inc., Eil Lilly, Roche, and AstraZeneca. V. Karantza, W. Pan, Z. Guo: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. J. Cortés: Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Financial Interests, Personal, Other, Honoraria (self), Travel / Accommodation /Expenses: Novartis; Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy: Celgene; Financial Interests, Personal, Other, Honoraria (self), Advisory /Consultancy: Eisai; Financial Interests, Personal, Other, Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria (self): Samsung; Financial Interests, Personal, Other, Advisory / Consultancy: Cellestia, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Financial Interests, Institutional, Other, Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Financial Interests, Institutional, Other, Research grant / Funding (institution): Ariad Pharmaceuticals, Baxalta, GMBH/Servier Affaires, Bayer Healthcare, F. Hoffman-La Roche, Guardanth Health, Merck Sharp & Dohme, Piqor Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Shareholder / Stockholder / Stock options: MedSIR. All other authors have declared no conflicts of interest.